Antonius M Vandongen

Antonius M Vandongen
Duke-NUS Medical School · Neuroscience and Behavioral Disorders Research Program

Ph.D.

About

101
Publications
15,090
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3,913
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Introduction
Antonius M VanDongen currently works at the Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School. Antonius is interested in mechanism underlying learning and memory.
Additional affiliations
December 2007 - present
Duke-NUS Medical School
Position
  • Professor (Associate)
January 1991 - December 2007
Duke University Medical Center
Position
  • Professor (Associate)
January 1991 - December 2007
Duke University
Position
  • Professor (Associate)

Publications

Publications (101)
Article
Full-text available
Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF...
Article
Full-text available
Arc is an immediate-early gene whose genetic ablation selectively abrogates long-term memory, indicating a critical role in memory consolidation. Although Arc protein localizes to neuronal synapses, it also localizes to the neuronal nucleus, where its function is less understood. Nuclear Arc forms a complex with the β-spectrin isoform βSpIVΣ5 and a...
Article
Full-text available
The ability to process complex spatiotemporal information is a fundamental process underlying the behavior of all higher organisms. However, how the brain processes information in the temporal domain remains incompletely understood. We have explored the spatiotemporal information-processing capability of networks formed from dissociated rat E18 cor...
Article
Full-text available
Short-term memory refers to the ability to store small amounts of stimulus-specific information for a short period of time. It is supported by both fading and hidden memory processes. Fading memory relies on recurrent activity patterns in a neuronal network, whereas hidden memory is encoded using synaptic mechanisms, such as facilitation, which per...
Article
Full-text available
In both humans and animals brief synchronizing bursts of epileptiform activity known as interictal epileptiform discharges (IEDs) can, even in the absence of overt seizures, cause transient cognitive impairments (TCI) that include problems with perception or short-term memory. While no evidence from single units is available, it has been assumed th...
Article
Advances in the development of three-dimensional (3D) brain organoids maintained in vitro have provided excellent opportunities to study brain development and neurodegenerative disorders, including Alzheimer's disease (AD). However, there remains a need to generate AD organoids bearing patient-specific genomic backgrounds that can functionally reca...
Preprint
Full-text available
New tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding...
Preprint
Full-text available
The immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hip...
Preprint
Full-text available
Advances in the development of three-dimensional (3D) brain organoids maintained in vitro have provided excellent opportunities to study brain development and neurodegenerative disorders, including Alzheimer's disease (AD). However, there remains a need to generate AD organoids bearing patient-specific genomic backgrounds that can functionally reca...
Article
Humans have a large capacity of recognition memory (Dudai, 1997), a fundamental property of higher-order brain functions such as abstraction and generalization (Vogt and Magnussen, 2007). Familiarity is the first step towards recognition memory. We have previously demonstrated using unsupervised neural network simulations that familiarity detection...
Preprint
Full-text available
The immediate-early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Arc protein is localized to excitatory synapses, where it controls AMPA receptor endocytosis, and to the nucleus, where it associates with Tip60, a subunit of a chromatin modifying complex. Here we show that Arc interacts with...
Article
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Background: Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA a...
Article
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C.-H. Yang’s appeared incorrectly on the original publication of this article.
Article
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Bacopa monnieri is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa’s nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identi...
Data
List of neuronal mRNAs that were differentially regulated by Bacopa. (XLSX)
Article
Full-text available
Humans instantly recognize a previously seen face as “familiar.” To deepen our understanding of familiarity-novelty detection, we simulated biologically plausible neural network models of generic cortical microcircuits consisting of spiking neurons with random recurrent synaptic connections. NMDA receptor (NMDAR)-dependent synaptic plasticity was i...
Data
Document S1. Supplemental Experimental Procedures, Figures S1–S3, and Tables S1–S3
Article
Full-text available
Although mutations in several genes with diverse functions have been known to cause amyotrophic lateral sclerosis (ALS), it is unknown to what extent causal mutations impinge on common pathways that drive motor neuron (MN)-specific neurodegeneration. In this study, we combined induced pluripotent stem cells-based disease modeling with genome engine...
Article
Full-text available
Background MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important post-transcriptional regulators of neuronal and synaptic development. The precise impact of miRNAs on presynaptic function and neurotransmission remains, however, poorly understood. Results Here, we identify miR-27b—an abundant neuronal miRNA implicated in neuro...
Article
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The fact that Parkinson’s disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling to advance our understanding of PD progression a...
Article
Full-text available
Cellular functions of the Golgi are determined by the unique distribution of its resident proteins. Currently, the electron microscopy is required for the localization of a Golgi protein at the sub-Golgi level. We have developed a quantitative sub-Golgi localization method based on centers of fluorescence masses of nocodazole induced Golgi mini-sta...
Article
Full-text available
Mutations in the human X-linked gene MECP2 are responsible for most Rett syndrome (RTT) cases, predominantly within its methyl-CpG-binding domain (MBD). To examine the role of MBD in the pathogenesis of RTT, we generated two MeCP2 mutant constructs, one with a deletion of MBD (MeCP2-ΔMBD), another mimicking a mutation of threonine 158 within the MB...
Article
Full-text available
Rett syndrome is a neurodevelopmental disorder that usually arises from mutations or deletions in methyl-CpG binding protein 2 (MeCP2), a transcriptional regulator that affects neuronal development and maturation without causing cell loss. Here, we show that silencing of MeCP2 decreased neurite arborization and synaptogenesis in cultured hippocampa...
Article
Full-text available
ABSTRACTA new,algorithm ispresented foridealizing single channel datacontaining anynumberofconductance levels. Thenumberoflevels andtheir amplitudes donothavetobeknowna priori. Noassumption hastobemadeaboutthe behavior ofthechannel, other thanthat transitions between conductance levels arefast. Thealgorithm isrelatively insensitive tothecomplexity...
Article
Full-text available
Spike timing-dependent plasticity (STDP) is a temporally asymmetric form of Hebbian plasticity in which the sign and magnitude of synaptic strength is determined by the precise timing between pre- and postsynaptic spikes. Postsynaptic NMDA receptors (NMDARs) play an important role in STDP due to their characteristic magnesium ion (Mg2+) gating pro...
Article
The Liquid State Machine (LSM) is a biologically plausible computational neural network model for real-time computing on time-varying inputs, whose structure and function were inspired by the properties of neocortical columns in the central nervous system of mammals. The LSM uses spiking neurons connected by dynamic synapses to project inputs into...
Article
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This paper presents a deterministic and adaptive spike model derived from radial basis functions and a leaky integrate-and-fire sampler developed for training spiking neural networks without direct weight manipulation. Several algorithms have been proposed for training spiking neural networks through biologically-plausible learning mechanisms, such...
Article
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Metastasis is the main cause of cancer mortality. During this process, cancer cells dislodge from a primary tumor, enter the circulation and form secondary tumors in distal organs. It is poorly understood how these cells manage to cross the tight syncytium of endothelial cells that lines the capillaries. Such capillary transmigration would require...
Article
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Experimental studies of neuronal cultures have revealed a wide variety of spiking network activity ranging from sparse, asynchronous firing to distinct, network-wide synchronous bursting. However, the functional mechanisms driving these observed firing patterns are not well understood. In this work, we develop an in silico network of cortical neuro...
Article
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L-aspartate α-decarboxylase (ADC) belongs to a class of pyruvoyl dependent enzymes and catalyzes the conversion of aspartate to β-alanine in the pantothenate pathway, which is critical for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb). Its presence only in micro-organisms, fungi and plants and its absence in anim...
Data
Binding poses of known inhibitors/ligands. The known inhibitors or ligands are shown as thick ball and stick. Atoms are colored as: H: white, C: green, N: blue, O: red and S: yellow. The interacting MtbADC residues are drawn as thin wireframe with the same color scheme and are labeled. Hydrogen bond interactions are shown as dotted yellow lines, al...
Data
Pantothenate and CoA biosynthesis pathway. L-Aspartate α-decarboxylase (ADC) catalyzes the decarboxylation of L-aspartate to β-alanine. (TIFF)
Data
The 28 ligand hits from the Maybridge, NCI and FDA databases which interact with at least one of the conserved functional residues of MtbADC residues involved in substrate binding and their glide score (kcal/mol). The ligands are ranked according to their glide scores in their respective databases. The ligands that interact with Pyr25 are in bold....
Data
The structures of known and reported inhibitors against ADC. (TIFF)
Data
Fumarate binding in ADC. (a) The superimposed view of the TthADC:fumarate crystal structure (red) and MtbADC:fumarate docking model (blue) is shown. The processed model for MtbADC was generated from the crystal structure of unprocessed protein and docking of fumarate was achieved using the Glide Extra Precision mode. The interacting conserved resid...
Data
Ligands docked to monomeric MtbADC. The structures of the top three hits, obtained by docking the Maybridge, NCI and FDA databases with the processed monomeric MtbADC structure. These molecules are big and cannot be genuine inhibitors as the actual active site is formed in the cleft of a dimer with relatively smaller volume and only molecules of sm...
Data
The ADMET properties of the 28 ligands. The ligands that interact with Pyr25 are in bold. The entries of Table 2 are underlined. The definitions of the properties are as in Table 2. (DOCX)
Data
Interactions of selected known inhibitors/ligands with MtbADC as verified by Glide XP. (DOCX)
Article
Full-text available
Metastasis of cancer cell was studied using microfluidic device. Migration of cells in the microchannel array mimics their transmigration in tissue capillaries during in vivo metastasis. Details of the morphological changes were recorded through high resolution imaging. Results showed that the deformation of cell nucleus is critical for the transmi...
Article
This paper reports a microfluidic platform for culturing neuronal networks and the study of axonal protein trafficking. The device consists of cultural microchambers connected by microchannel array. Molecular biological methods were used to express fluorescent proteins in neurons. Preliminary results show that the neurons can be polarized with thei...
Article
In this paper, we present a microfluidic platform for the study of cancer cell transmigration and anti-cancer drug screening. The device consists of an array of microchannels with dimensions close to the capillaries on the cellular barriers, while a thin glass coverslip is used as the substrate to enable high resolution imaging of cell dynamics dur...
Conference Paper
Full-text available
Music Information Retrieval (MIR) is an interdisciplinary field that facilitates indexing and content-based organization of music databases. Music classification and clustering is one of the major topics in MIR. Music can be defined as `organized sound'. The highly ordered temporal structure of music suggests it should be amendable to analysis by a...
Chapter
NMDA receptors (NMDARs) are glutamate-gated cation channels with high calcium permeability that play important roles in many aspects of the biology of higher organisms. They are critical for the development of the central nervous system (CNS), generation of rhythms for breathing and locomotion, and the processes underlying learning, memory, and neu...
Conference Paper
Full-text available
Spiking neural networks have been shown capable of simulating sigmoidal artificial neural networks providing promising evidence that they too are universal function approximators. Spiking neural networks offer several advantages over sigmoidal networks, because they can approximate the dynamics of biological neuronal networks, and can potentially r...
Article
Full-text available
N-Methyl-D-aspartate (NMDA) receptors play a critical role in both development of the central nervous system and adult neuroplasticity. However, although the NMDA receptor presents a valuable therapeutic target, the relationship between its structure and functional properties has yet to be fully elucidated. To further explore the mechanism of recep...
Article
Full-text available
Although the N-methyl-D-aspartate (NMDA) receptor plays a critical role in the central nervous system, many questions remain regarding the relationship between its structure and functional properties. In particular, the involvement of ligand-binding domain closure in determining agonist efficacy, which has been reported in other glutamate receptor...
Article
Full-text available
Arc/Arg3.1 is an immediate early gene whose expression is necessary for the late-phase of long-term potentiation (LTP) and memory consolidation. Whereas pathways regulating Arc transcription have been extensively investigated, less is known about the role of post-transcriptional mechanisms in Arc expression. Fluorescence microscopy experiments in c...
Book
The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written...
Article
Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is an immediate early gene, whose expression in the central nervous system is induced by specific patterns of synaptic activity. Arc is required for the late-phase of long-term potentiation (LTP) and memory consolidation, and has been implicated in AMPA receptor trafficking. Since Arc'...
Article
Full-text available
K+ channels achieve exquisite ion selectivity without jeopardizing efficient permeation by employing multiple, interacting K+-binding sites. Introduction ofa cadmium (Cd2+)-binding site in the external vestibule of Kv2.1 (drk1), allowed us to functionally characterize a binding site for external monovalent cations. Permeant ions displayed higher af...
Article
Full-text available
Abnormalities in dendritic spines have long been associated with cognitive dysfunction and neurodevelopmental delay, whereas rapid changes in spine shape underlie synaptic plasticity. The key regulators of cytoskeletal reorganization in dendrites and spines are the Rho GTPases, which modify actin polymerization in response to synaptic signaling. Rh...
Article
Full-text available
Voltage-gated K channels assemble from four identical subunits symmetrically arranged around a central permeation pathway. Each subunit harbors a voltage-sensing domain. The sigmoidal nature of the activation kinetics suggests that multiple sensors need to undergo a conformational change before the channel can open. Following activation, individual...
Article
Maintenance of synaptic plasticity requires protein translation. Because changes in synaptic strength are regulated at the level of individual synapses, a mechanism is required for newly translated proteins to specifically and persistently modify only a subset of synapses. Evidence suggests this may be accomplished through local translation of prot...
Article
Full-text available
Juvenile neuronal ceroid lipofuscinosis (JNCL) is due to mutations in the CLN3 gene. We previously determined that CLN3 protein harbors a highly conserved motif, VYFAE, necessary for its impact on cell growth and apoptosis. Using molecular modeling we demonstrated that this motif is embedded in a stretch of amino acids that is homologous to and str...
Article
Protein transport to and from the postsynaptic plasma membrane is thought to be of central importance for synaptic plasticity. However, the molecular details of such processes are poorly understood. One mechanism by which membrane and secretory proteins may be transported to and from postsynaptic membranes is via cargo receptors. We studied the den...
Article
Full-text available
The interaction of an agonist with its receptor can be characterized by two fundamental properties, affinity and efficacy. Affinity defines how tightly the agonist associates with its receptor, and efficacy measures the ability of the bound ligand to activate the receptor. Although affinity and efficacy are independent properties, the binding and a...
Article
Full-text available
Spinophilin/neurabin II is an actin-associated scaffolding protein enriched in the dendritic spines of neurons. Previously, the actin-binding domain (ABD) of spinophilin was localized to a domain between amino acids (aa) 1 and 154. In a mass spectrometry screen for spinophilin-binding proteins, we have identified an additional actin-binding region...
Article
Because NMDA receptors play critical roles in both neuronal survival and plasticity, their expression levels need to be carefully controlled. The number of functional NMDA receptors is temporally and spatially regulated at a hierarchy of levels, from gene transcription to protein trafficking. In this review we will focus on mechanisms for controlli...